NHGRI's Epigenetics Investments Starting to Pay Off

Manolis Kellis, professor of computer science at MIT, addressed the Bio-IT
World Conference on efforts to revolutionize the study of human disease by
bridging the gap between genetics and epigenetics.

Kellis uses genomic datasets to discover relationships between single
nucleotide polymorphisms (SNPs) and epigenetic regulation. Previously, these
data sets of genomic variation were used to derive associations between SNPs
and specific diseases in so-called genome-wide association studies (GWAS).
Kelliss research goes one step further. We wanted to find out what the
molecular mechanism is for this association, he said.

Over the past five years, there has been an explosion of research on the
statistical associations between specific SNPs and the likelihood an
individual would get a disease. This paradigm led researchers to look for
specific genes that caused a disease phenotype. The list of contributing genes
for complex diseases, such as Crohns disease or type 2 diabetes, can run into
the dozens, yet only explain a fraction of the heritability of the diseases.

What Kelliss research shows, though, is that diseases are actually caused by
subtle contributions from a huge number of regulatory variants. If we rank all
the SNPs based on the association with a disease, Kellis said, we find that
there are not 10 or 20, but thousands of regions that weakly contribute to the
disease.

WHEN SCIENTISTS SEQUENCED the human genome a decade ago, they hoped to
unlock the code of life, the sequence of molecules lined up in every cell
that, summed together, made a person a personand possibly reveal new ways to
understand and treat diseases. But the results turned out to be opaque.
Biologist Eric Lander, who helped lead the effort, famously summed up the
results in seven words: Genome: Bought the book; hard to read.

So the research community went looking for CliffsNotes. A decade ago
scientists started looking into the epigenome, chemical modifications to DNA
that tell cells which genes to turn on or turn off. This week that project got
a huge data dump24 journal articles laying out what the genomicists know so
far about 111 different cell types, the inner lives of brains, hearts, blood,
and skin. It is giving us a view of the living, breathing genome in motion, as
opposed to a static picture of DNA, says Manolis Kellis, a computational
biologist at MIT who worked on three1 of the new papers.

Just about every cell in a human body has the same DNA, packaged into the same
chromosomes. But cells differentiate, growing into different tissue types with
different functions. The epigenome works through molecules like methyl and
acetyl groups that wheedle their way into DNA, exposing different genes to the
machinery that reads them and makes proteins. That helps control when or
whether those proteins get made at all, and its also critical to that process
of differentiation. In each cell type, it unravels just the right genes, says
Brad Bernstein, a biologist at Harvard University. It unravels just the right
switches.

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Since then, the world had seen a boom of ‘convincing’ epigenetics studies
explaining all kinds of human troubles. A few examples are given below.

Trauma Has Genetic Impact for Native Americans

Native American communities across the United States are struggling with
poverty, alcoholism, high rates of diabetes, PTSD and depression.
Historically, these issues have been attributed to systemic problems like
racism that makes it challenging to leave the reservation, but recent research
suggests the issues facing the Native American community run deeper than that.
So much deeper, in fact, that theyre found within their genes, thanks to a
fascinating pattern of genetic evolution and inheritance known as epigenetics.

The Holocaust is still traumatizing the children of survivors on a genetic level

World War II saw countless crimes against Jews. Millions were killed, and
those who survived had their lives permanently scarred. But the harm may not
have stopped there. A new study has found that the trauma experienced by
Holocaust survivors caused genetic changes, which can be passed down to their
children.

Epigenetic ‘tags’ linked to homosexuality in men

The biology of sexual orientation has been one of the most vexing and
politically charged questions in human genetics. For the first time,
researchers have found associations between homosexuality and markers attached
to DNA that can be influenced by environmental factors.

Twin studies and family trees provide strong evidence that sexual orientation
is at least partly genetic. When one identical twin is gay, there is about a
20% chance that the other will be as well1. But because this rate is not 100%,
it is thought that environmental factors play a role as well. One of the best
characterized is the ‘older brother effect’: the chance of a man being gay
increases by 33% for each older brother he has2. The reason is not clear,
although one hypothesis holds that the mothers immune system begins to react
against male antigens and alter the fetuss development.

Doctors using epigenetics to treat migraines

One in four people suffer from migraine headaches and often they’re sent to
their optometrist to see if the cause is vision related.

At Dr. Scott Sedlacek’s eye center in Olmsted Falls, OH he’s using epigenetics
to get to the root cause of the headache.

XR Epigenetic testing is a cheek swap and a small blood sample.

It tells you what foods are right for your body chemistry but also what you’re
missing.

Dr. Sedlacek has been offering this testing for the past three years.

“Most people are eating foods that are not thought to be bad, but they’re bad
for them because we’re all so unique and individual,” Sedlacek said.

Dr. George Rozakis is a bioengineer and ophthalmologist.

“We have an astonishing rate of 97 percent success. We did a study in 34
patients. Thirty-three of the 34 had a profound improvement. They were all
very difficult to treat migraine patients,” Rozakis said.

Rozakis says epigenetics is not new. It’s been studied for various health
conditions, including ADHD, Autism and Lupus.